PubMed Health⌕ Search

Biomedical subjects

D Zauli

Publications and source records attributed to D Zauli.

At least 19 recordsLinked to original sources
PubMed1997

Anti-neutrophil cytoplasmic antibodies in type 1 and 2 autoimmune hepatitis.

Perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) have been recently defined as the most sensitive autoantibody of type 1 autoimmune hepatitis (AIH-1). Their prevalence in type 2 autoimmune hepatitis (AIH-2) has not yet been evaluated. The aim of the present study was to verify the association of pANCA with AIH-1 in an Italian series and to investigate the prevalence of the antibodies in AIH-2 and in proper control groups represented by cases of chronic hepatitis C (CH-C) with similar autoimmune features. pANCA were found in 30 of 46 (65%) AIH-1 and in 4 of 30 (13%) ANA/smooth muscle antibody (SMA) positive CH-C (P = .0000006). Nineteen AIH-2, 29 liver kidney microsomal antibody type 1/liver cytosol antibody type 1 (LKM1/LC1) positive CH-C cases and 50 healthy controls were all negative. In AIH-1, pANCA were significantly (P = .009) more frequent in males (8 of 9, 89%) than in females (22 of 37, 59%). All pANCA positive sera showed SMA of the antiactin type. The present data confirm that pANCA, although less prevalent in our series than in other reports, do associate with AIH-1 also in the Mediterranean area and show that it can identify a small subgroup (13%) of ANA/SMA positive chronic hepatitis C, in which autoimmune reactions might play a more relevant role than viral infection. They also show the antibodies are absent in AIH-2. In conclusion, pANCA appear to be mutually exclusive of LKM1 positivity, either hepatitis C virus-related or not, thus representing a further valuable tool to differentiate the two types of autoimmune hepatitis.

Adolescent↗
PubMed1997

Quantitative liver parameters of HCV infection: relation to HCV genotypes, viremia and response to interferon treatment.

BACKGROUND/AIMS: This study aimed to evaluate the relation between the number of hepatocytes positive for HCV antigens and the amount of HCV RNA in the liver and to evaluate the relationship between the above parameters and viremia levels, HCV genotype and response to interferon treatment. METHODS: This was a retrospective study on 31 consecutive patients with chronic HCV-related liver disease, selected on the basis of the availability of frozen liver tissue for both liver HCV antigens detection and liver HCV RNA quantitation. HCV antigens (immunohistochemistry), liver and plasma HCV RNA (competitive RT-PCR), and HCV genotype (commercial kit) were studied. RESULTS: A significant correlation (p=0.0005) was found between the amount of liver HCV RNA (log 10 copy/microg of extracted RNA) and the number of HCV-infected hepatocytes (scored from 0 to 3). These parameters were not significantly correlated with viremia levels. The highest liver HCV RNA levels and HCV antigen scores were found in patients infected with genotype 1b. Liver HCV RNA (median 541 x 10(3) vs 118 x 10(3) copy number/microg, p=0.031) and liver HCV antigens (mean score 2.3 vs 1.3, p=0.018) but not plasma HCV RNA (median 14956 x 10(3) vs 2885 [correction of 2.885] x 10(3) copy number/ml, ns) were significantly higher in patients not responding to interferon treatment compared to responders. CONCLUSIONS: The tissue parameters tested in this study were significantly correlated, shared the same clinical implications and predicted short-term response to interferon treatment better than viremia levels. We suggest that these tests should be included in the study protocol of patients under evaluation for interferon treatment, basing the choice on local facilities.

Adult↗
PubMed1997

Ultrasound-detected abdominal lymphadenopathy in chronic hepatitis C: high frequency and relationship with viremia.

BACKGROUND/AIMS: This study aimed to investigate the prevalence and significance of ultrasound-detected deep abdominal lymphadenopathy in chronic hepatitis due to C virus. METHODS: One hundred and thirty-four consecutive patients with various liver disorders were examined with portable real-time equipment. RESULTS: In 25 (19%), the procedure failed because of excessive meteorism. Deep nodes, mainly located in the hepato-duodenal ligament, were detected in 62 of the remaining 109 patients (57%), reaching the highest prevalences in primary biliary cirrhosis (5/7, 71%), chronic hepatitis C (44/66, 67%) and autoimmune hepatitis type 1 (2/3, 67%). For all patients, including those with liver diseases with multiple etiology, lymphadenopathy was more frequent in anti-HCV positive (51/81, 63%) than in negative cases (11/28, 39% p=0.02). In chronic hepatitis C, serum HCV RNA was detected by nested polymerase chain reaction in all 31 patients with, but in only 75% (12/16) of those without nodes (p=0.018). No other distinct clinical or laboratory feature was found in association with lymphadenopathy; in particular, its incidence was similar in cases with and without liver cirrhosis. CONCLUSIONS: Enlarged deep abdominal lymph nodes are frequently detected by ultrasound in patients with chronic hepatitis C. This feature may be of diagnostic utility, especially in early cases, when liver cirrhosis has not yet developed and therefore no other ultrasound sign of the underlying disease can be detected. Lymphadenopathy may be of biological significance, marking hepatitis C virus infection in a replicative, viremic stage. These observations support the existence of a close interaction between hepatitis C virus and the lymphatic system.

Abdomen↗
PubMed1996

Impact of international autoimmune hepatitis group scoring system in definition of autoimmune hepatitis. An Italian experience.

We have reclassified 110 patients with autoantibody-positive cryptogenic chronic hepatitis according tot he aggregate scoring system proposed by the International Autoimmune Hepatitis Group for signs of hepatitis C virus (HCV) infection and the newly proposed terminology of "unclassified" chronic hepatitis. Anti-HCV and HCV viremia were assessed by second-generation assays and reverse transcription-polymerase chain reaction. Immunomorphological and immunochemical characterizations of antinuclear, smooth, muscle, liver-kidney microsomal type 1, and liver cytosol type 1 autoantibodies were also performed. All 45 anti-HCV negative patients fulfilled the score criteria for the diagnosis of "definite" or "probable" autoimmune hepatitis (AIH). Eight anti-HCV-positive cases reached the score of "probable" AIH, whereas the remaining 57 cases were diagnosed as unclassified chronic hepatitis. The scoring system allows the correct identification of all autoimmune cases without HCV infection. Autoimmune hepatitis runs a more severe disease course than unclassified chronic hepatitis, whose clinical and histological features are similar to those of autoantibody-negative chronic hepatitis C.

Adolescent↗
PubMed1996

Low hepatitis C viremia levels in patients with anti-liver/kidney microsomal antibody type 1 positive chronic hepatitis.

BACKGROUND/AIMS: The majority of adult patients positive for anti-liver-kidney microsomal antibody are also positive for anti-hepatitis C virus and serum HCV RNA. In these patients the role played by hepatitis C virus infection in the progression of liver damage and its relationship with anti-liver-kidney microsomal antibody are, however, still a matter of debate. METHODS: To clarify this point we have compared hepatitis C viremia in sera from 31 hepatitis C virus-related chronic hepatitis patients positive for anti-liver-kidney microsomal antibody with that of 31 patients with hepatitis C virus-related chronic hepatitis without autoantibodies using a newly developed competitive reverse transcription-polymerase chain reaction technique. Reverse transcription-polymerase chain reaction was performed using a synthetic competitor of a length similar to that of wild template (71 bp vs 86 bp). RESULTS: The results obtained have been related to hepatitis C virus genotypes. Anti-liver-kidney microsomal antibody/anti-HCV positive patients show a median value of hepatitis C virus genome molecules (626829/ml, range 9780-25651424), significantly lower than anti-liver-kidney microsomal antibody negative/anti-HCV positive patients (10158314/ml, range 101822-67429974) (p < 0.001). No hepatitis C virus genotype was significantly associated with anti-liver-kidney microsomal antibody, although a predominance of genotype 1 (subtypes a and b) has been observed in these patients. CONCLUSIONS: Since a low hepatitis C viremia has been observed in anti-liver-kidney microsomal antibody positive patients with disease severity comparable to that of patients without autoantibodies, it is conceivable that in them autoimmune mechanisms may cooperate with viral infection in sustaining disease activity.

Adolescent↗
PubMed1995

Hepatitis C virus (HCV) genotype, tissue HCV antigens, hepatocellular expression of HLA-A,B,C, and intercellular adhesion-1 molecules. Clues to pathogenesis of hepatocellular damage and response to interferon treatment in patients with chronic hepatitis C.

To obtain information on the mechanisms of hepatocellular damage and the determinants of response to interferon, hepatitis C virus (HCV) genotype, tissue HCV antigens, hepatocellular expression of HLA-A,B,C and intercellular adhesion-1 molecules, and the number of lobular T lymphocytes were studied in 38 anti-HCV-positive patients. 14 patients did not show a primary response to interferon treatment. HCV genotype 1b was detected in 11 of them. They displayed higher scores of HCV-positive hepatocytes, HLA-A,B,C, and ICAM-1 molecules expression than with the responders. HCV-infected hepatocytes maintained the capacity to express HLA-A,B,C and ICAM-1 molecules. CD8-positive T cells in contact with infected hepatocytes and Councilman-like bodies were observed. A significant correlation was found between the number of lobular CD8-positive T cells and alanine amino transferase levels. No differences were observed in clinical, biochemical, and histological features between patients with high and low number of hepatocytes containing HCV antigens. These data suggest a prominent role of T cell-mediated cytotoxicity in the genesis of hepatocellular damage. The high expression of interferon-inducible antigens like HLA-A,B,C molecules suggests the presence of strong activation of the interferon system possibly related to high HCV replication in nonresponder patients infected with genotype 1b.

Antigens, Viral↗
PubMed1995

Hepatocellular codistribution of c100, c33, c22, and NS5 hepatitis C virus antigens detected by using immunopurified polyclonal spontaneous human antibodies.

Hepatitis C virus (HCV) antigens in liver biopsy have been detected by immunohistochemistry using both spontaneous human IgG and murine monoclonal or rabbit polyclonal monospecific reagents. Conflicting results have been obtained in different studies. This was probably because of the incapacity of single experimental antibodies, raised against synthetic or recombinant peptides, to recognize native tissue antigens. To overcome this possibility, we immunopurified monospecific spontaneous polyclonal human Ig, therefore induced by native antigens, from the single antigen-containing bands of RIBA 3 strips. Antibodies to c100, c33, c22, and NS5 antigens were obtained from the serum of a patient affected by chronic hepatitis C. The IgG fraction of this serum had proved to stain tissue HCV antigens. Eight biopsies were selected on the basis of strong hepatocellular reactivity with the whole IgG fraction in a variable number (from 5% to 75%) of cells. The four antigens were detected in all biopsies; a clear cellular codistribution was observed on serial sections. These data demonstrate that the possibility to identify HCV antigens in liver biopsies is higher when using human antibodies induced by native antigens rather than experimental antibodies. The approach of immunopurification of human antibodies can be extended to other HCV-related epitopes to obtain reagents useful for the selection and optimization of monoclonal or polyclonal antibodies.

Antigens, Viral↗
PubMed1994

Increased risk of hepatocellular carcinoma development in patients with cirrhosis and with high hepatocellular proliferation.

The immunohistochemical determination of the accessory protein of DNA-polymerase delta (PCNA), a marker of an early S-phase of the cell cycle, was used to evaluate cell proliferation retrospectively in formalin-fixed, paraffin-embedded liver biopsy sections in a group of patients with cirrhosis of similar age and duration of follow up, and with no evidence of hepatocellular carcinoma (41), including 17 patients with and 24 without hepatocellular carcinoma appearance during follow up. Proliferation was expressed as total (PCNA-TOT) and strongly (PCNA-STRO) positive nuclei per 1000 hepatocytes. The presence of dysplasia was also recorded. Histological findings and biochemical data, at the time of liver biopsy, were compared in the two groups. While total PCNA positivities were not significantly different in the two groups, strong reactivity was significantly higher in patients who eventually developed hepato-cellular carcinoma (median 0.7 vs 2.6). Univariate analysis of histological and biochemical data at the time of biopsy, followed by a stepwise regression study, showed that the significant parameters for a time-dependent disease-free state were, in decreasing order: cholesterol, PCNA-STRO, PCNA-TOT and alpha foeto-protein. Other clinical, biochemical and histological parameters, including dysplasia, provided no further information. From these data, hepatocellular proliferation can be evaluated in patients with cirrhosis with a currently available technique. Patients with high cell proliferation are at increased risk of developing hepatocellular carcinoma and may require differentiated follow up.

Adult↗
PubMed1994

Interferon therapy in liver/kidney microsomal antibody type 1-positive patients with chronic hepatitis C.

The association between liver/kidney microsomal antibody type 1 and adult cases of hepatitis C virus-related chronic liver disease has been firmly established. In the presence of both markers, evidence of autoimmunity (liver/kidney microsomal antibody type 1) and actual viremia (serum HCV RNA), the therapeutic dilemma arises between steroids, which are beneficial to autoimmune but deleterious to viral diseases, and interferon-alpha, which may exacerbate an autoimmune disorder. Six patients with liver/kidney microsomal antibody type 1 and serum HCV RNA were given interferon-alpha: three showed a response pattern similar to that observed in autoantibody-negative chronic hepatitis C cases; the other three developed a sharp transaminase peak, which was not followed by HCV RNA clearance. Considering the brisk flare-up of liver cell necrosis, interferon-alpha treatment proved to be dangerous in the above three liver/kidney microsomal antibody type 1/HCV RNA positive cases. Subsequent steroid administration reduced alanine aminotransferase peaks, but may be harmful in viral infections. Therapeutic alternatives are needed: they will probably include pure antivirals (exerting no immunostimulatory effects) with or without immunosuppressive drugs.

Adolescent↗
PubMed1994

Hepatocellular expression of HLA-A, B, C molecules predicts primary response to interferon in patients with chronic hepatitis C.

Primary response rate to alpha-interferon (IFN) is about 50% in patients with chronic hepatitis C. Criteria for predicting a positive primary response are lacking. HLA-A,B,C molecule expression is known to be stimulated by viral infections. In 36 consecutive interferon-treated anti-HCV positive patients with an available frozen liver biopsy sample, the predictive value of liver HLA-A,B,C expression, and of histologic, clinical, and biochemical parameters was evaluated. Response to treatment was defined by normalization of transaminases, and disappearance of serum HCV-RNA within 3 months. According to these criteria, 17 patients were classified as nonresponders and 19 were classified as responders. The pattern of HLA-A,B,C hepatocellular positivity varied from normal (negative or occasional faint staining of hepatocellular membranes) to diffuse, strong "honeycomb" positivity. The highest scores of positivity were found in nonresponder patients. The discriminant capacity of HLA-A,B,C scores of positivity was compared with clinical, biochemical and histologic parameters by discriminant analysis. HLA-A,B,C expression was found to be the main discriminant parameter, in addition to alkaline phosphate (ALP) and gamma-glutamyl-transpeptidase (GGT) which added little additional information. The higher hepatocellular expression of class I MHC molecules in nonresponder cases may reflect a different viral effect on hepatocytes, which is induced by different HCV genotypes or levels of viremia. From a clinical point of view, the pretreatment HLA-A,B,C pattern of positivity represents a powerful tool in the selection of patients for interferon treatment.

Adult↗
PubMed1992

Demonstration of peptide-specific and cross-reactive epitopes in proteins reacting with antimitochondrial antibodies of primary biliary cirrhosis.

Recently the main targets of antimitochondrial antibodies (AMA) of primary biliary cirrhosis have been identified as parts of three related mitochondrial multienzyme complexes, namely pyruvate dehydrogenase (PDH), branched chain alpha-ketoacid dehydrogenase (BKDH) and alpha-ketoglutarate dehydrogenase (alpha-KGDH). Usually AMA-positive PBC serum samples show reactivity to more than one of these, raising the question whether they are exclusively different antibodies or are, at least in part, the result of cross-reactive specificities. With Western immunoblotting, four antigens with molecular masses of 74, 52, 51 and 43 kDa, are recognized by PBC sera. In this study, using affinity purified antibodies from mitochondrial proteins immobilized on nitrocellulose blots, we demonstrate the presence of peptide-specific and cross-reactive epitopes in some targets. In particular, at least three different epitopes present in the 74-kDa protein (presumed to by PDH-E2) are also present in the 51-kDa protein (probably PDH-X), and two in the 52-kDa peptide (possibly BCKDH-E2). Moreover, the 43-kDa mitochondrial protein (the identity of which is more problematic) has three epitopes. One of these is also present in the 74-, 52- and 51-kDa proteins, a second in the 74- and 51-kDa, and a third seems to be peptide-specific. These results show that different sera with the same immunoblotting pattern of reactivity can have antibodies with different antigenic specificities and, conversely, that the same specificity can be responsible for more than one band.

Adult↗
PubMed1992

Serum autoantibodies and the diagnosis of type-1 autoimmune hepatitis in Italy: a reappraisal at the light of hepatitis C virus infection.

Antinuclear antibodies with the homogeneous pattern (ANA-H) and smooth muscle antibodies with antiactin specificity (SMA-AA) are regarded as the serum markers of type-1 autoimmune chronic hepatitis. Their diagnostic relevance, however, has been questioned recently after the detection of signs of hepatitis C virus infection in autoimmune chronic hepatitis patients. To further evaluate this point, antihepatitis C virus antibodies were sought by two second generation assays (ELISA 2 and RIBA 2) in 100 Italian patients with chronic liver disease of unknown aetiology, including 46 with (autoimmune chronic hepatitis) and 54 without the above antibodies (cryptogenic). By ELISA 2, antihepatitis C virus, although significantly prevalent in cryptogenic (83%), were found also in a substantial proportion of autoimmune chronic hepatitis patients (46%) (p < 0.0001), their occurrence was confirmed by RIBA 2 in almost all cases (96% and 86%, respectively). Autoimmune patients with either ANA-H or SMA-AA exhibited similar antihepatitis C virus prevalences (59% and 52%, respectively); by contrast, the eight cases positive for both the autoantibodies were consistently antihepatitis C virus negative. These findings confirm that in countries with high hepatitis C virus circulation (like Italy) an overlap between autoimmune chronic hepatitis and hepatitis C virus infection, reflected by 'true' antihepatitis C virus antibodies, does occur. The detection of ANA-H or SMA-AA, in fact, identifies chronic liver disease patients with a relatively low prevalence of antihepatitis C virus, but does not exclude hepatitis C virus infection. Positive findings for both ANA-H and SMA-AA, however, is an appropriate marker for hepatitis C virus free 'primary' autoimmune chronic hepatitis.

Actins↗
PubMed1991

Anti-nuclear antibodies of primary biliary cirrhosis recognize 78-92-kD and 96-100-kD proteins of nuclear bodies.

The specificities of anti-nuclear antibodies (ANA) reacting with multiple nuclear dots (MND-ANA) present in about 15% primary biliary cirrhosis sera were studied by Western blot analysis with nuclear fractions from a human cell line. Reactivity with two broad bands of 78-92 kD and 96-100 kD of the insoluble fraction was present exclusively in MND-ANA-positive sera. Antibodies eluted from these proteins specifically retained the immunofluorescence reactivity of MND-ANA. Immunomorphological analysis by a pre-embedding technique revealed that the antibody specifically binds to nuclear regions resembling in size and number nuclear bodies. Since these structures are absent in immature rate endometrial cell and can be induced by diethylstilbestrol, we tested MND-ANA by immunofluorescence on cryostat sections of uteri from hormone-treated and untreated immature rats. A strong reaction of nuclear dots was observed predominantly in endometrial cells of hormone treated rats. We thus conclude that MND-ANA present in primary biliary cirrhosis sera are directed against 78-92-kD and 96-100-kD nuclear proteins located in nuclear bodies.

Animals↗
PubMed1990

Anti-actin antibodies: a new test for an old problem.

Smooth muscle antibodies with anti-actin specificity are commonly regarded as markers of autoimmune liver disease. However, there are interpretational problems because different techniques have been used for their identification and therefore the results are difficult to compare. The present paper reports the results of a new method for the identification of anti-actin antibodies (indirect immunofluorescence on cryostat sections of liver from rats chronically injected with phalloidin). The results have been compared with those obtained by four other techniques: demonstration by immunofluorescence of kidney peritubular reactivity (SMAT), of anti-microfilament antibodies (on HEp-2 cells and vinblastine-treated peripheral blood mononuclear cells) and counterimmunoelectrophoresis with purified muscle actin as antigen. The new method proved to be the most sensitive and specific. Furthermore, its reproducibility was found to be high, the interpretation easy and the cost low. The clinical significance of anti-actin antibodies in patients with chronic liver disease is also discussed.

Actins↗